Oxime carbamate phosphate,phosphonate,phosphinate and phosphoroamidates

ABSTRACT

OXIME CARBAMATE PHOSPHATE, PHOSPHONATES, PHOSPHINATES AND PHOSPHOROAMIDATES HAVING THE GENERAL FORMULA:   (R-P(=X)(-R1)-Y-),Q,(R4-S-COO-N=C(-R2)-)BENZENE   IN WHICH X AND Y ARE INDEPENDENTLY SELECTED FROM THE GROUP CONSISTING OF OXYGEN AND SULFUR; R IS SELECTED FROM THE GROUP LOWER ALKYL OR LOWER ALKOXY, HAVING FROM 1 TO 6 CARBON ATOMS INCLUSIVE; R1 IS SELECTIVE FROM THE GROUP CONSISTING OF LOWER ALKYL OR LOWER ALKOXY HAVING FROM 1 TO 6 CARBON ATOMS, INCLUSIVE, AMINO, LOWER ALKYL-SUBSTITUTED AMINO AND PHENYL; Q IS SELECTED FROM THE GROUP CONSISTING OF DIVALENT TETRAMETHYLENEDIENE-1,3, LOWER ALKOXY OR LOWER ALKYL HAVING FROM 1 TO 4 CARBON ATOMS INCLUSIVE,EACH, NITRO, HALOGEN AND COMBINATIONS THEREOF, AND LOWER DIALKYL-SUBSTITUTED THIONOPHOSPHORYLOXY; R2 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, LOWER ALKYL HAVING FROM 1 TO 4 CARBON ATOMS, AND PHENYL; R4 IS LOWER ALKYL HAVING FROM 1 TO 4 CARBON ATOMS, INCLUSIVE, AND B-CHLORO-LOWERALKYL HAVING FROM 2 TO 4 CARBON ATOMS. THE COMPOUNDS ARE USEFUL AS INSECTICIDES, ANIMAL CONTACT AND SYSTEMIC PARASITICIDES, HERBICIDES AND FOLIAR FUNGIPROTECTANTS.

United States Patent US. Cl. 260-455 P 2 Claims ABSTRACT OF THEDISCLOSURE Oxime carbamate phosphates, phosphonates, phosphinates andphosphoroamidates having the general formula:

in which X and Y are independently selected from the group consisting ofoxygen and sulfur; R is selected from the group lower alkyl or loweralkoxy, having from 1 to 6 carbon atoms inclusive; R is selected fromthe group consisting of lower alkyl or lower alkoxy having from 1 to 6carbon atoms, inclusive, amino, lower alkyl-substituted amino andphenyl; Q is selected from the group consisting of divalenttetramethylenediene-1,3, lower alkoxy or lower alkyl having from 1 to 4carbon atoms inclusive, each, nitro, halogen and combinations thereof,and lower dial-kyl-substituted thionophosphoryloxy; R is selected fromthe group consisting of hydrogen, lower alkyl having from 1 to 4 carbonatoms, and phenyl; R is lower alkyl having from 1 to 4 carbon atoms,inclusive, and p-chloro-loweralkyl having from 2 to 4 carbon atoms.

The compounds are useful as insecticides, animal contact and systemicparasiticides, herbicides and foliar fungi protectants.

This application is a division of application Ser. No. 49,933, filedJune 25, 1970, now US. Pat. 3,652,737, which in turn was a division ofcopending application Ser. No. 730,588, filed May 20, 1968, nowabandoned which application is a continuation-in-part of then copendingapplication Ser. No. 646,467, filed June 16, 1967, now abandoned.

This invention relates to certain novel phosphorus containing compoundswhich can be used as insecticides, animal parasiticides, both contactand systemic, herbicides and foliage fungi protectants. Morespecifically, this invention relates to certain substituted organo-oximephosphates, phosphonates, phosphinates and phosphoroamidates and to thepreparation and utility of the compounds as insecticides, animalsystemic parasiticides, herbicides and foliage fungicides.

The compounds comprising the instant class of compounds correspond tothe general formula:

in which X and Y are independently selected from the group consisting ofoxygen and sulfur; R is selected from the group lower alkyl or loweralkoxy, having from 1 to 6 carbon atoms, inclusive; R is selected fromthe group consisting of lower alkyl or lower alkoxy having from 1 to 6carbon atoms, inclusive, amino, lower alkyl-substituted amino, andphenyl; Q is selected from the group consisting of divalenttetramethylenediene-1,3, lower alkoxy or lower alkyl having from 1 to 4carbon atoms inclusive, each, nitro, halogen and combinations thereof,and lower dialkyl substituted thionophosphoryloxy; R is selected fromthe group consisting of hydrogen, lower alkyl having from 1 to 4 carbonatoms and phenyl; and R is selected from the group consisting ofhydrogen substituted carbonate and thiocarbonates of the type in which Zis oxygen or sulfur, R is lower alkyl having from 1 to 4 carbon atoms,inclusive, and B-chloroloweralkyl having from 2 to 4 carbon atoms;carbamates of the type in which R and R are independently selected fromthe group consisting of hydrogen, alkyl having from 1 to 10 carbons,inclusive, substituted alkyl having 1 to 6 carbon atoms inclusive, saidsubstituent is selected from the group consisting of hydroxy, halogen,amino, di-lower alkyl amino, lower alkoxy and tetrahydrofuryl; loweralkenyl having from 2 to 4 carbons, inclusive, carboal-koxy alkyl havinga total of from 3 to 8 carbon atoms, inclusive, cycloalkyl having from 3to 6 carbon atoms, inclusive, piperazino, 2-thiazolyl, phenyl, naphthyl,substitnted phenyl wherein said substituents are selected from the groupconsisting of halogen, lower alkyl, lower alkoxy, lower thioalkyl, lowerdialkylamino in which said lower alkyl and lower alkoxy moieties havefrom 1 to 4 carbon atoms, inclusive, nitro, cyano, trifluoromethyl andcombinations thereof; and in which is an N-containing heterocyclicmember selected from the group consisting of morpholino, piperazino,pyrrolidino, piperadino, hexamethylenamino, pyrryl, indolyl, imidazolyl,benzimidazolyl, pyrazolyl, 1,3-oxazolidino, and 1,3-thiazolidino; estersof the type wherein R is selected from the group consisting of alkylhaving from 1 to 8 carbons, inclusive, trichloromethyl, and loweralkenyl having from 2 to 4 carbon atoms, inclusive, and the radical (CHSR in which m is l or 2, R is alkyl having 1 to 6 carbon atoms, alkenylhaving 2 to 4 carbon atoms, phenyl, substituted phenyl in which saidsubstituents are selected from the group halogen, lower alkyl having 1to 4 carbon atoms, inclusive and lower alkoxy having 1 to 4 carbonatoms, inclusive; lower alkyl sulfonato having from 1 to 6 carbon atoms,inclusive; lower alkyl substituted thiophosphoryl wherein the loweralkyl groups independently contain from 1 to 4 carbon atoms, inclusive;and 2,2,2-trichlorol-hydroxyethyl, 4-cyanophenyl, 2,4,5-trichlorophenyland 4-methylthiophenyl. Lower alkyl and lower alkoxy includes thosemembers of the groups which contain the indicated number of carbon atomsin both straight chain and branched chain configurations. Lower alkenylincludes those members of the group containing a double bond andcontaining from 2 to 4 carbon atoms, inclusive. When Q is divalenttetramethylene-l',3 it is bonded to the 2,3 or 3,4 carbon atoms of thephenyl ring, thereby becoming either a or 3 naphthyl, respectively. Alsoincluded herein is a method of preparing, using, and applying thecompositions.

The compound herein described can be prepared by several methods. Onesuch general method applicable in preparing the compounds is thecondensation between the appropriate substituted phosphorus-containingoxy or thio benzaldehyde, e.g. phosphoro, phosphono, and phosphino, andhydroxylamine hydrochloride in order to prepare the correspondingbenzaldoxime. The benzaldoxime can be further reacted with appropriatesubstituted isocyanate, substituted acid chlorides, substitutedchloroformate, substituted chlorothioformate, substituted sulfonylchloride, monosubstituted carbamyl chloride, N,N-disubstituted carbamylchloride, substituted phosphoryl chloride, substituted thionophosphorylchloride, or anhydrous trichloroacetaldehyde. When R is to be loweralkyl, an appropriate substituted-phosphoryl orsubstituted-thiophosphoryl lower alkyl phenylketone is condensed withhydroxylamine hydrochloride to prepare the corresponding ketoxime.Another method useful for the preparation of carbamyl derivatives isfirst the condensation of phosgene with the aldoximine followed by thecondensation with a primary or secondary amine. The reactions proceedreadily in the liquid phase. The employment of a solvent is also useful,facilitating processing, as well as agitation of the reactants. Solventssuch as water, benzene, toluene, chloroform, aqueous ethanol and thelike, can be employed. When using derivatives containing the aldoxime,it is preferred to carry out the reaction in the presence of a hydrogenhalide acceptor such as sodium carbonate, triethylamine, pyridine,picoline and the like, which are used as catalysts. Similarly, in thecondensation reaction to prepare secondary carbamyl derivatives, thereaction is preferably conducted in the presence of a hydrogen halideacceptor.

The reactions are carried out at temperatures that permit operation inthe liquid phase. These temperatures are between about room temperatureand reflux temperature of the solvent, if one is employed. Preferably,the reaction mixture is refluxed, usually at an elevated temperature.The ketoxime can be reacted with functional moieties as described suprafor the benzaldoxime.

It now has been discovered that the new compositions disclosed hereinare distinguished as useful as insecticides, herbicides, foliar fungiprotectants and are particularly effective as systemic parasiticidalagents for animals.

The compounds of the present invention are prepared in accordance withthe following illustrative examples.

EXAMPLE 1 Preparation of the intermediate3-[O-(0,0-diethylphosphorothioyl)] benzaldehyde In 200 ml. of methylethyl ketone in a 500 ml. 3-neck flask are combined 24.4 g. (0.2 mole)3-hydroxybenzaldehyde, 37.8 g. (0.2 mole)0,0-diethylthiophosphorylchloride, and 16.4 g. (0.12 mole) potassiumcarbonate. The mixture is stirred and heated under reflux for 4 hours,cooled, and poured into 300 ml. of water. The mixture is filtered freeof solid and is extracted with two 150 ml. portions of chloroform. Thechloroform phases are combined, dried with anhydrous MgSO and thesolvent evaporated. There is obtained 54.7 g. (99.5 percent of theory)of the title intermediate, n =1.5239.

Preparation of 3-[0,0-diethylphosphorothioyl] benzaldoxime In 300 ml. ofwater are combined 27.4 g. (0.1 mole) 3-[O-(0,0-diethylphosphorothioyl)]benzaldehyde and 7.6 g. (0.1 mole) hydroxylamine hydrochloride. Themixture is stirred at room temperature, and 7.5 g. (0.06 mole) sodiumcarbonate monohydrate is added over a period of 20 min. The resultingmixture is stirred at room temperature for 1 hour. The mixture isextracted with 2-150 ml. portions of benzene. The benzene phases arecombined,

4 dried with anhydrous MgSO and evaporated. There is obtained a yield of20.0 g. (68.3% of theory) of the title compound, n =1.5460.

EXAMPLE 2 Preparation of3-[0,0,0-diethylphosphorothioyl)]benzaldoximino-N'-methyl carbamate Tengrams (0.034 mole) of 3-[0 (O diethylphosphorothioyl) ]-benzaldoximedissolved in 10 ml. of acetone is treated with an excess ofmethylisocyanate. The mixture is poured into 200 ml. of benzene. Thebenzene is washed with 2-50 ml. portions of water, dried with anhydrousMgSO and evaporated. There is obtained a yield of 11.2 g. (93.3 percentof theory) of the title compound, 11 1.5394.

EXAMPLE 3 Preparation of 4-[O-(0,0-diethylphosphorothioyl)]-acetophenone oxime In 150 ml. of percent aqueous ethanol are combined56.2 g. (0.195 mole) 4-[O-(0,0-diethylphosphorothioyl)]-acetophenone,17.4 g. (0.25 mole) hydroxylamine hydrochloride, and 4 gms. (0.1 mole)sodium hydroxide. The mixture is heated and refluxed for 5 min., cooled,acidified with concentrated hydrochloride acid and extracted with twoml. portions of chloroform. The chloroform phases are combined, driedwith anhydrous MgSO and evaporated. There is obtained 55.0 g. (93.5percent of theory) of the title compound, n 1.5393.

EXAMPLE 4 Preparation of 4-[O-(0,0-diethylphosphorothioyl)]-acetophenoneoximino-N'-methyl carbamate By an analogous procedure asgiven in Example 2, supra, 10.0 g. (0.03 mole) of4-[O-(0,0-diethylphosphorothioyl)]-acetophenoneoxime is reacted withmethyl isocyanate. There was obtained 11.5 g. (96.9 percent of theory)of the title compound.

EXAMPLE 5 Preparation of4-[0,0-diethylphosphorothioyl]-acetophenoneoximino acetate The followingprocedure also can be used with a carbamyl chloride, sulfonyl chlorideor chloroformate in order to obtain compounds that include therespective functional moieties typical of said reactants.

In 150 ml. of benzene 10.0 g. (0.03 mole) of 4-[4-(0,O-diethylphosphorothioyl)]-acetophenoneoxime, 3.2 g. (0.04 mole) ofacetylchloride, and 4.1 g. (0.04 mole) of triethylamine are combined.The mixture is heated and refluxed for about one hour. The cooledreaction mixture is washed with two 50 ml. portions of water. Thebenzene phase is dried with anhydrous magnesium sulfate and then thebenzene evaporated. There is obtained 11.0 g. (96.5 percent of theory)of the title compound n =1.5279.

EXAMPLE 6 Preparation of 4-[O-(0,0-diethylphosphorothionyl)]benzaldoximino-N'-morpholinylcarbamate Seven grams (0.07 mole) ofphosgene in 150 m1. of anhydrous diethyl ether is added to a 500 ml.3-neck flask fitted with a stirrer, dropping funnel, Dry Ice condenser,and thermometer. The solution is stirred and cooled to 10 C. with an icebath. N,N-dimethylaniline, 8.6 g. (0.07 mole) is added over a period of30 minutes. 4-[O-(0,0- diethylphosphorothioyl)] benzaldoxime, 14.5 g.(0.05 mole) in 50 ml. of anhydrous diethyl ether is added over a periodof 30 minutes. The temperature of the reaction mixture is maintainedbetween 10 and 15 C. After the addition is complete, the mixture isstirred for one hour at 15 C. A solution of 17.4 grams (0.2 mole) ofmorpholine and ml. of water is added to the stirring reaction mixture atsuch a rate that the temperature does not exceed C. After the additionis complete, the mixture is stirred for two hours at room temperature.The mixture is diluted with 200 ml. of ether and washed consecutivelyEXAMPLE 8 Preparation of4-[0-(0,0-diethylphosphorothioyl)]benzaldoximino-N'[fl-(N"-diethylamino)ethyl]carbamate 5 Seven m 0.07 l f hos e e, 8.6 a s 0.07 with 100 ml. ofwater, 100 ml. 1 N HCl, and agaln with 1 gm S m0 ext? p g H gr m 00 1 fTh th h h nh d mo e) of N,N-d1methylan1l1ne, and 14.5 grams (0.05 1 m 0water 3 e er P ass 18 led wlt a y mus mole) of 4-[0-(0(odimethylphosphorothioyl)]benzald- Mgso4 evaporated to yleld 18 grams(893% of oxime are reacted in 200 ml of anh drous diethyl ether-diethylphosphorothioyl)] benzaldoxy P [0 (01,0 b 1 542 by the proceduredescrlbed 1n Example 6. The etherical lmmoN morphohnylcar amate 10solution is washed with ml. of ice cold 1 N HCl and EXAMPLE 7 returnedto the reaction flask where it is stirred and cooled Preparation of4-[0(0,0-diethylphosphorothioyl)]bent9 10 A i grams mole). of 2 all do d0X eth 1) carbamate dlethyl ethylened1am1ne and 10 ml. of water 1s addedto mm B y r y y the etherical solution at such a rate that thetemperature Seven grams (0.07 mole) of phosgene, 8.6 grams (0.07 15 doesnot exceed 15 C. After the addition is complete, the mole) of N,Ndimethylaniline and 14.5 grams (0.05 mixture is stirred at roomtemperature for one hour. An mole) of 4-[O-(0,0-diethylphosphorothioyl)]benzaldadditional 100 ml. of anhydrous diethyl ether is added, oxime arereacted in 200 ml. anhydrous diethyl ether by and the mixture is washedwith 50 ml. of ice cold 1 N the procedure described in Example 6. Theetherical solu- NaOH followed by two 50 ml. portions of water. The tionis cooled to 10 C. and a solution of 6.1 grams (0.1 0 ether phase isdried with anhydrous MgSO and evapmole) of ethanolamine and 10 m1. ofwater is added at orated. There is obtained 11.3 grams (51.8% of theory)such a rate that the temperature does not exceed 15 C. of the titlecompound, n =1.5310. After the addition is complete, the mixture isstirred at The following is a table of the compounds prepared acroomtemperature for one hour. The product is isolated cording to theaforedescribed procedures. Compound by the procedure described inExample 6. There is oh- 5 numbers have been assigned to each compoundand are tained a 17.8 gram (94.8% of theory) of the title comthen usedfor identification throughout the balance of the pound, n =1.5423.application.

TABLE I /PY R R J=N0---R3 d l l li R R1 x Y R5 M.P.( 0.) ,55

021150 s 0 H H 1.5450. 2H5 S O 1.5520. CzH5O s 0 H G(O)NHCH5- 1.5394.0511 0 S O C(0)NHCH3 94-96 deec. 0411 0 B 0 C(O)NHGH2CH=CH2. 1.5430.021150 B 0 H 1.5405. C2H50 S 0 0( s- 1. 5318 041150 8 0 C(O)NHOH 1.5354.0.1150 s 0 C(O)NHOH2GH- 1.5330, C2H5O S 0 C(O)NH(CH2)3CH3 1.5255. 055150B 0 O(O)HCC15 1.545s. 01-130 S o 1.5555. 05130 S o O(0)NHCHa. 1.553s.CHaO S O 1.5494. 01130 s o C(O)NHCH3 1.5400. 01130 s 0 C(O)NHCH(CH1)21.5247. 01150 s 0 C(O)NHCH(CH3)2-. 1.5427. 021150 8 0 H 1.5410. 021150 50 O(O)NHCH5 1.5435. 051150 B o C(O)NHCH2CH=CH2 1. 5303. 01140 s 0 01330s 0 041150 5 0 05150 s 0 05150 s 0 1.5323. 021 B 0 1.5094. 021150 8 01.5340. 01150 s 0 1.5592. 01140 s 0 1.5527 021150 s o .5393 021150 S 0Dark oil: CzHsO S 0 )N 1.5382. {5150 s 0 1.5203. 05130 s 0 )N 1.5195.0H50 s 0 15128. 021150 5 0 O)NH 1.5163. 01150 s 0 )NHCHz 1.5055. 01130 s0 C(O)NHOH(CH3)2 1.537s. 021150 8 o O(O)NHCH5 1.5485. 01130 s o C(O)CH5.1.5543. 021150 8 o C(O)CH3...-- 1.5410. C4H5O s 0 C(O)NHCH5 1.5413.021150 s o C(O)NHGH2OH=CH2.-- 1.5307. 0515150 3 o 0 0)0H3 1.5305. 0211505 0 0(o 00m. 5.5055. 021150 5 0 C(O)NHC1H1. 1.5354. 0211 0 B OC(0)NHCHa. 1.5502. 021150 5 o 0 CH3 1.5279. 02115 s 0 C(O)NHCH(CH3)21.5334. 02115 s 0 C(O)NHCH2(OH2)(OHz)CHa 1.5372. 021150 3 0 0 0 004H11.5117 C1115 S O 021150 B O 2H5 S O 02:55 S O 28. CzHs S 0 1.5461. 05150S 0 H H H3 851111511110. 01150 8 0 H C(0)NHCH2OH=CH1 1.5503.

See footnote at end of table.

TABLE I-Continued Com ound num er mmmmmmmmmmmmmmmmrnmmmmmmmmmmmmmmmwmmmN OO'QOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO n4 tastpw-wmmm-pwmw mmmihpwn wmwammarms-tmmc- N(CH3)1 1.5270. NH-3-OH S-phenyl 1.6090. )NH(O H1) 1.5425.

Waxy solid; 1.5574. 1.5186. 1.5128. H H9) 1.5564 H. C(O)NH(CH2CH=CH2)1.5777. H C(O)NH-3-CH S-pl1eny1 1.6105. H. C(O)NH-4-Br-pheny1. 1.5998. H0 Si l-99. H C(O)NH(i-O3H 1.5274. H C(O)CHiS-4-Cl-phenyl 1.6077. H do1.5703. H O(O)NH-3-CF -phenyl H C(O)NH(CH l 4 C(O)NH(CH3) 4 H C(O)NH(3-CS heny 1. 4 C(O)NH(CHzCH=CH 1.5463 4 CH C(O)NH(C4H9) 1.5493. 4 CH3..."C(O)NH(3-CF -phenyl) 1.5632. 4 H do 1.5507.

l 1 (p) =position of phenyl substitution by [C=N0-R relative to thephosphorus containing group.

HERBICIDAL SCREENING TESTS Novel compositions are phytotoxic compoundswhich are useful and valuable in controlling various plant species.

In the method of the present invention for controlling undesirableplants which comprises applying an herbicidally eifective amount of theabove-described compounds to the area in which control is desired, anherbicide is used to mean a compound which controls or modifies thegrowth of plants. By an herbicidally effective amount is meant an amountof compound which causes a modifying eifect upon the growth of plants.Such modifying effects include all deviations from natural development,for example, killing, retardation, defoliation, desiccation, regulation,stunting, tillering, stimulation, dwarfing and the like. By plants it ismeant germinant seeds, emerging seedlings, and established vegetationinluding the roots and above-ground portions.

The compounds of this invention were tested as herbicides in thefollowing manner.

Pre-emergence herbicide test-The seeds of crab grass (CG) (Digitariasanguinalis (L) Scop.), foxtail (Ft) (Setaria glauca (L.) Beauv.),watergrass (WG) (Echinm chloa crusgalli (L.) Beauv.), pigweed (PW)(Amaranthus retroflexus (L.), mustard (Md) (Brassicw juncea (L.) Coss.),and curly dock (CD) (Rumex crisp us (L.) were planted in individual rowsone-half inch deep in Santa Cruz sandy loam soil contained in compressedpaper flats 8% x 6 /2", which are 2%" deep. Enough seeds were planted togive about thirty to fifty plants of each of the weed species in eachflat. The flats were watered after planting. The following day each flatwas sprayed at the rate of pounds of the candidate compound under testin 80 gallons of solution per acre. An atomizer was usedto spray thesolution on the soil surface. The flats were placed in a greenhouse at80 F. and watered regularly. Two weeks later the degree of weed controlwas determined by comparing the amount of germination and growth of eachweed in the treated flats with weeds in several untreated control flats.The results of this test are reported in Table II.

Post-emergence herbicide test.The seeds of four weed species, crab grass2(CG) (Digitaria sanguinalis (L) Scop.), watergrass (WG) (Echinochloacrusgalli (L.) Beauv.), red oats (R0) (Avena sativa (L.)), mustard (Md)(Brassica juncea (L.) Coss.), and one crop, pinto beans PB) (Phaseolusvulgaris) were planted in individual rows as described in thepre-emergence test, supra. Two weeks after planting, the plant foliagewas sprayed with a 0.5% solution of the test compound at a rateequivalent to 12.5 pounds/ acre. The treated plants were placed back inthe greenhouse. Injury ratings were recorded 14 days after treatment.The rating system is the same as that used in the pre-emergence test.Table III lists the results obtained therefrom.

TABLE II.PRE-EMERGENOE HERBICIDE TEST1 Compound number C G Ft WG PW MtCD 5.- 10. 11 12-- 15.. it" iii iii 1 28 "1L. ii 1;"- 41:: 42-- 43..46.- 41 48 49- 50.- 52. 54-- 55-- 56.... a "11 a. it 60:- g; i++ 711-137- g i+ 1411 14 1 Herbieidal activity rating.i-=slight injury;=moderate injury; +++=severe injury or death.

TABLE IIL-POST-EMERGENCE HERBICIDE TESTI Compound number CG WG R Md PBiii ii" i i++ 17 1s- 20. 21 23- 24.. 27.- 28 9 3 33 at iii in it.

iii "+11" a iii n 1. 65-- 6G 68- 133 134-- 12;- iii 138. 11% i+ L iiiiii+ 1 1 Herbieidal activity ratin'g.+=slight injury; ++=moderateinjury; =severe in ury or death.

The compounds of the present invention are used as pro-emergence orpost-emergence herbicides and are applied in a variety of ways atvarious concentrations. In practice, the compounds are formulated withan inert carrier, utilizing methods well known to those skilled in theart, thereby making them suitable for application as dusts, sprays, ordrenches and the like in the form and manner required. The mixtures canbe dispersed in water with the aid of a wetting agent or they can beemployed in organic liquid compositions, oil and water in oil emulsions,with or without the addition of wetting, dispersing or emulsifyingagents. The amount applied depends upon the nature of the seeds orplants to becontrolled and the rate of application varies from 1 toapproximately 50 pounds per acre.

The phytotoxic compositions of this invention are applied to the plantsin the conventional manner. Thus, the dust and liquid compositions canbe applied to the plant by the use of power-dusters, boom and handsprayers and spray-dusters. The compositions can also be applied fromairplanes as a dust or a spray because they are effective in very lowdosages. In order to modify or control growth of germinating seeds oremerging seedlings, the dust and liquid compositions are applied to thesoil according to conventional methods and are preferably distributed inthe soil to a depth of at least /2 inch below the soil surface. It isnot necessary that the phytotoxic compositions be admixed with the soilparticles and these compositions can be applied merely by spraying orsprinkling the surface of the soil. The phytotoxic compositions of thisinvention can also be applied by addition to irrigation water suppliedto the field to be treated. This method of application permits thepenetration of the compositions into the soil as the water is absorbedtherein. Dust compositions, granular compositions or liquid formulationsapplied on the surface of the soil can be distributed below the surfaceof the soil by conventional means such as discing, dragging or mixingoperations.

The phytotoxic compositions of this invention can also contain otheradditaments, for example, fertilizers, pesticides and the like, used asadjuvant or in combination with any of the above-described adjuvants.Phytotoxicants useful in combination with the above-described compoundsinclude for example 2,4-dichlororophenoxyacetic acids,2,4,S-trichlorophenoxyacetic acid, 2-methyl-4- chlorophenoxyacetic acidand the salts, esters and amides thereof; triazine derivatives, such as2,4-'bix(3-methoxypropylamino) 6 methylthio-S-triazine; 2 chloro-4-ethylamino 6 isopropylamino-S-triazine, and 2-ethylamino 4-isopropylamino 6 methylmercapto-S- triazine; urea derivatives, such as3-(3,4-dichlor0phenyl)- 1,1 dimethyl urea and 3 (p-chlorophenyl)1,1-dimethyl urea, and acetamides such as N,N-diallyl-a-chloroacetamide,N (a-chloroacetyl)hexamethylene imine, and N,N-diethyl-a-bromoacetamide,and the like; benzoic acids such as 3 amino 2,5 dichlorobenzoic and;thiocarbamates, such as S-propyl dipropylthiocarbamate; S-ethyldipropylthiocarbamate, S ethyl-cyclohexylethylthiocarbamate,S-ethyl hexahydro-lg-azepine-l-carbothioate and the like. Fertilizersuseful in combination with the active ingredients include, for example,ammonium nitrate, urea and superphosphate. Other useful additamentsinclude materials in which plant organisms take root and grow such ascompost, manure, humus, sand and the like.

The compositions of the present invention were tested as foliagefungicides. This test indicated protectant action against fungiattacking plant foliage. Pinto bean plants were sprayed with threeconcentrations of dissolved or suspended chemical in water, 1000, 500and 100 parts per million (p.p.m.). The active compound was dissolved inan appropriate solvent and further dispersed in water, and for thispurpose a surface active agent or wetting agent was employed tofacilitate formulation of the dispersions. After the sprayed plants weredried, they were inoculated with powdery mildew spores (Erysiphepolygoni). Results were read when disease symptoms were distinct onuntreated bean plants. Compound numbers 84 and 86 exhibited 75-99%control at 100 p.p.m. and compound number exhibited control at 100 p.p.mof the powdery mildew infection with no phytotoxicity.

Insecticidal evaluation tests The following insect species weresubjected to evaluation tests for insecticidal activity:

( 1) Housefiy (HF)-Musca domestica' (Linn.)

(2) German roach (GR)Blattella germanica (Linn.)

(3) Salt-marsh caterpillar (SMC)EStigmene acrea (4) Milkweed bug(MWB)Onc0peltus fasciatus (Dallas) (5) Lygus bug (LB)Lygus hesperus(Knight) Aliquots of the toxicants, dissolved in an appropriate solvent,were diluted in water containing 0.002% of a wetting agent, Sponto 221(a polyoxyether of alkylated phenols blended with organic sulfonates).Test concentrations ranged from 0.1% downward to that at which 50%mortality was obtained. In the tests, for these species, 10 one-monthold nymphs of the German cockroach and Lygus bug and two-week old nymphsof milkweed bug were placed in separate circular cardboard cages sealedTABLE IV-Con'tinued 13 on one end with cellophane and covered by a clothnetting on the other. Test concentrations for the Lygus Bug ranged from0.05% downward to that at which 50% t 5583511 1 31111131 5111 m 000 0 0mmmmou oM 0 u o o m mmmm m mm Wm 00 0 00 0 .0 0 0 000000 0 .0 00 0 a D 1L 5 W 7 m It 55533515558115. 158 55 .1 4 a mm 00000m000 M Sc00000000..00.0.0 0. ...0. 7 M 0 00 0 0 0 000 0 0 0 0 00 00 m 6 p e 9 m.4 it 1111111115333333311111513111 3 n m 000u00000 0 0000o u aoo m mmmmmm m d m m 0 m D u u m b m d m n T @W fi78587856773730774855555656454430338954 278 0 0 r c 5 2 W n fl k r u g H 0 O u. m P m m tIu III IIIIILI I w H n n i w r n n n a d r 6 g e O b n u a f m H n n .mu u g a n n u u u .mum7 d u u N U n n m m u n a h e 0 0 t I. 0 p 1 m u mn n u u u i45 s 7 s0 1 2 0.5... aa7 s 2 3 2 6 0 890 00 0 1 222 e G 07fl%m%mmmmmm1 1nn111 mmmmmmmmm r 5 mortality was obtained. Each of theaqueous suspensions of the candidate compounds were sprayed onto theinsects through the cloth netting by means of a hand spray gun.

' Percent mortality in each case recorded after 72 hours and the LD-SOvalues expressed as percent of toxicant in the aqueous spray wasrecorded.

For testing the Salt Marsh Caterpillar, test solutions were prepared inan identical manner and at concentrations the same as for the Germancockroach and the milkweed bug above. Sections of bitter dock (Rumexobtusifolus) leaves, 1-1.5 inches in length were immersed a wire screento dry. The dried leaf was placed on a moistened piece of filter paperin a Petri dish and infested with 5-3rd Instar larvae. Mortality of thelarvae was recorded after 72 hours and the LD-SO values are expressed aspercent active ingredient in the aqueous 126 suspension.

The following procedure was used to test houseflies.

A stock solution containing 100 ug/ml. of the toxicant in an appropriatesolvent was prepared. Aliquots of this solution were combined with 1milliliter of an acetonepeanut oil solution in a glass Petri dish andallowed to dry. The aliquots were there to achieve desired toxicantconcentration ranging from 100 ,ag. per Petri dish to that at which 50%mortality was attained. The Petri dishes bottom with cellophane andcovered on top with cloth netting. Twenty-five female houseflies wereintroduced into the cage and the percent mortality was recorded after 48hours. The LD-50 values are expressed in terms of pug. per 25 femaleflies. The result of these insecticidal evaluation tests are given inTable IV.

TABLE IV (LD- Values) 0.03%; compound number 64l0.05%; compound number68-0.08% and compound number 54-0.008

HE, GR, 8M0 Com 0 d b t 1 r 1' h t 1 t t p on num er 1s ex reme y use umt e con ro percen percen percen of European corn borer (Pyraustanubilalis (Hubner)).

Compound number t etg t l mwmdmnv om mmmwmmmm mmmwm fim o ...mwg mm armf w we osmo O .1 a 0 a SP am n. U I I0 S. mv W h 00 Ma 6 mmWW h .w m% mm mcmw i wmmwmfi nan .m%m m fi cou) mu 0 w m m .4 we vwmn ne 2. a 5 mm umm m u Kfif e m &O n MM 300% 0 2. ..i? a D .1 O G .m wfi m wma amfi m ooa mm wehn n mno a omyf o fiuo mm w u m U m mm eam ma a ..%w w m c H65.00 0 0U(St.t. 5 m fW H o w m m flawo mvwmno m mtne 1( f S ISV W 0 V52fl h) w hS 001D m 0 00 e d( .ml 5 0 f O a E m 3 n PW 1 yp ob r/. O ..I(\.w H m Rm. D% a n mm smmmm m m m U M L- em H a... aw M 506 e 1 6 C H r ut. U L r. r. te7 M m CSX u a eae uh mfl m aepOa 5H3 V.O OaeGO 3) W W fiWA B O SCd w s pm s nco nh o y p 5 .S 5 u ...LSS na V .q 11 amon mm mamm m m m mm m m mm c ;w im. c uhgk t .1 1. 1.1 g011% 0m :1 t %O C)S H Od 0 S 6 as D 0 A P EIO.1W(10P .m 5 1 h 3 t mwBzW 0 m mT Omn ..D (d a .1o n o d ae d 0 a mmm w wmmw mmmw mmmm mm a m o 5 0 d m e m)n mun m m meh mm I re n ti m C .1 Ce a m aw X 6 aoc e m0 w h 0511B W61 05 lrsa .5mtwTc a tbPTttac bPuPweO T e a a e m 11555859011111111.111111111115185351111111131111158 .0m.0000000000000000000000000 000000000000000000MM 0 0 0 0 0 0 nw0 0 .0 0.0 0 0 Q0 0 Q0 0 0 0 0 0 0 00 0 .0 .0 0 0 011%M%11%1111111111111111111111111111111 M 111 00 .0 0.0QO0Q00000000000000000000000000 .0 .00

are administered orally by stomach tube at an initial dosage of 400 mg./kg. to fasted male Swiss albino mice.

88550 00 0500 88 u 8058000585000004885 ama maaaammmammmi 12 a 51 1.222..1

Two hours after treatment, the mice are killed by cervical dislocationand both thighs are dissected from each test animal and placed inlabeled glass vials. Each vial is inoculated with newly hached blackblow fly larvae (Phormia regina (Meigen)) and stored in an incubator at80 F. and 40-50% relative humidity. Tissues from mice that die duringthe two hour holding period after administration of the compounds areprocessed in the same manner. After the larvae had fed on the tissuesfor 48 hours, the vials are examined and the percentage of larvaemortality in each is noted. If 80% or more of the larvae are killed atthe initial dosage, successively lower dosages are then tested until thelowest dosage that killed at least 80% of the larvae is determined.

In this animal systemic insecticide evaluation test, compounds aretested further on guinea pigs, using the oral route of administration.The compounds are formulated as solutions or suspensions in Tween-20 andadministered at an initial dosage of 100 mg./kg. Twentyfour hours priorto treatment, the guinea pigs are wounded and the wounds infested withlarvae of the black blow fly (Phormia regina (Meigen)). At four andtwenty-four hours after treatment, stable flies (Stomoxys calcitrans(L.)) are fed on the guinea pigs. Engorged flies are held for 24 hoursto see if they are killed by the blood they ingest. At 24 hours aftertreatment, the wounds are examined to see if the fly larvae are killedby the insecticide. If the larvae are alive, they are removed from thewounds. If any of the arthropods are killed at the initial dosage, thecandidate insecticides are administered at lower dosages until there wasno significant insecticidal activity. The following table gives theresults of the mouse assay and guinea pig assay tests described above.

TAB LE V.AND\IAL SYSTEMIC INSECTICIDE ACTIVITY Lowest dosage (mg/kg.)

Mouse assay Guinea pig assay Lethal to mice s-I e) 80%+ Lethal to activeguinea pig s/ s-I e) Blow fly larvae (m -I e) Compound number Thecandidate compounds were employed in an in vitro tick assay. In thistest unfed lone star tick nymphs (Amblyomma americanum (L.)) wereconfied for 24 hours in cotton cloth that had been treated in acetonesolutions of the test compounds. The percentage of nymphal mortality wasthen observed. If 80% or more of the nymphs were killed at the initialscreening level of 1.0% for a given compound, the compound was testedfurther at lower levels. The compounds 5, 11, 17, 20, 23, 26, 31, 33,36, 38, 61, 64 and 65 exhibited 80% or better control of the tick nymphsat 0.5%. Compound number 29 exhibited 80% or better control of the ticknumphs at 0.1% and compound number 32 exhibited 80% or better control at1.0% concentrations. Compound number 28 at a concentration of 0.05% wasbetter than 80% lethal to tick nymphs.

Internal animal parasite systemic tests The following proceduresdescribe the chemoprophylactic and chemotherapeutic efiicacy testsutilized to demonstrate the animal arasitology activity of thephosphorus-containing oxime carbamate compositions of the presentinvention.

Test I.Unparasitized weanling mice were offered medicated food for 1-2days prior to inducing infections, and for a total of 21 days infectionswere administered per os using 100-300 embryonated ova/ mouse ofSyphacia obvelata (So) and 100300 embryonated ova/mouse of Aspiculuristetraplera (At).

A suitable number of unmedicated littermate mice also received the aboveinfection and served as control to determine the comparative efiicacy ofthe medications. All mice were sacrificed after 21 days (the medicationperiod) and the residual parasites found in the intestine wereidentified and counted. These counts in the medicated groups werecompared to the unmedicated (controls) and a percent efiicacy wasassigned, (M/ICX100)100=percent efficacy.

Test 2,-Weanling mice were housed together with older pinworm (So) and(At) infected mice in a box with damp litter for 15 to 21 days to allowa heavy pinworm infection containing all stages of oxyurid (So and At)to naturally build up. At the end of this holding period, thepost-weanling littermates were weighed individually and dosed with thesubject compounds (suspended in Tween 20) on a body weight basis. One to3 days later, these mice were sacrificed and the residual wormsidentified, counted and compared to the unmedicated controls. Examplesof efiicacy observed for six compounds of the present invention aregiven in the following table.

TABLE VI.INTERNAL ANIMAL SYSTEMIC ACTIVITY The test results indicatethat these compounds are biologically active and are useful as animalsystemic insecticides. The compounds can be used as effectiveparasiticides by applying them in a variety of ways and at variousconcentrations, depending upon the nature and habitat of the parasite tobe controlled.

Dosage- Percent eflicaey Test (1) ppm. or Compound number procedure (2)mgJkg. So At (1) 500 100 100 1 2,000 100 (2) 50 85 (2) 100 65 85 (1) 500100 100 (1) 1, 000 100 100 (1 1, 000 as 97 (1) 2,000 55 (2) 50 30 0 (2)100 45 30 (2) 200 55 100 (1) 250 100 100 (2) 5O 85 75 (2) 100 100 100(1) 1, 000 100 100 (2) 50 65 100 (2) 100 80 100 (2) 50 92 97 (2) 100 10098 500 100 100 (2) 5O 95 (1) 2, 000 100 50 70 85 (1) 1,000 98 100 (2) 5098 65 (l) 250 100 100 (2) 50 95 85 (1) 250 90 65 (2) 50 95 15 (1) 500100 100 (2) 50 55 92 TABLE VIContinued Dosage- Percent eflicacy Test (1)p.p.m. or Compound number procedure (2) mg. /kg. So At The compounds ofthe present invention are useful as elfective insecticides, herbicides,and external and internal animal parasiticides and are applicable in avariety of Ways at various concentrations. In practice, the compoundsare formulated with an inert adjuvant utilizing methods well known tothose skilled in the art, thereby making them suitable for applicationand administration as dusts, sprays, drenches and the like in the formand manner required. The mixtures can be dispersed in water with the aidof a wetting agent or they can be employed in organic liquidcompositions, oil-in-water, water-in-oil emulsions, with or without theaddition of wetting, dispersing or emulsifying agents. Administration ofsaid parasiticidal compositions to animal for systemic control ofparasites can be in animal feedstuffs which contain feed components ofsuch as grain, grasses and the like, and certain beneficial additivessuch as vitamins, proteins, fats, minerals and carbohydrates. They canbe given also in drinking water or skimmed milk, or in the form oftablets or capsules. Further methods of application include sprays,dyes, dips, dermal pouron, subcutaneous administration, intramuscularinjection and the like. The exact dose to be administered to the animalis dependent upon the parasite to be controlled by the particularcompound employed, as described herein, as well as upon whether theadministration is to be a single dose or a multiple dose over a periodof days. In general,

18 it has been found that the systemic parasiticides of this inventioncan be administered orally or parenterally to warm blooded animals inamounts ranging from about 0.01 to about 600 milligrams per kilogram ofbody Weight.

What is claimed is: 1. A compound having the formula in which X and Yare independently selected from the group consisting of oxygen andsulfur;

R is selected from the group lower alkyl or lower alkoxy,

having from 1 to 6 carbon atoms, inclusive;

R is selected from the group consisting of lower alkyl,

lower alkoxy having from 1 to 6 carbon atoms, inclusive, amino, loweralkyl-substituted amino and phenyl;

Q is selected from the group consisting of hydrogen, di-

valent tetramethylenediene-1,3-lower alkoxy or lower alkyl having from 1to 4 carbon atoms, inclusive, nitro and halogen; and lower dialkylsubstituted thionophosphoryloxy;

R is selected from the group consisting of hydrogen, lower alkyl havingfrom 1 to 4 carbon atoms and phenyl; and

R is selected from the group consisting of lower alkyl having from 1 to4 carbon atoms, inclusive, and ,8- chloroloweralkyl having from 2 to 4carbon atoms, inelusive.

2. A compound according to claim 1 in which R is C H O, R is C H O, X isS, Y is O and Q is H, and the group is in the nuclear 4-position inwhich R is CH and R4 is CH3.

References Cited UNITED STATES PATENTS 3,673,181 6/1972 Gutman 260-944LEWIS GOTTS, Primary Examiner R. L. RAYMOND, Assistant Examiner US. Cl.X.R.

